CFAP53

Chr 18AR

cilia and flagella associated protein 53

Also known as: CCDC11, HTX6

NCBI Gene: 220136ENSG00000172361UniProt: Q96M91

The CFAP53 protein is a microtubule inner protein component of cilia axonemes that regulates motile cilia beating and is required for both motile and non-motile cilium assembly. Mutations cause visceral heterotaxy-6, a disorder of left-right body asymmetry that typically presents in the neonatal period with complex congenital heart defects and abnormal organ positioning. This condition follows autosomal recessive inheritance.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Heterotaxy, visceral, 6, autosomal recessiveMIM #614779
AR
0
Active trials
4
Pubs (1 yr)
57
P/LP submissions
0%
P/LP missense
1.34
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— CFAP53
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 unique Pathogenic / Likely Pathogenic· 100 VUS of 212 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.34LOEUF
pLI 0.000
Z-score 0.10
OE 0.98 (0.72–1.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.58Z-score
OE missense 1.10 (1.00–1.21)
300 obs / 273.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.98 (0.72–1.34)
0≤0.351.4
Missense OE1.10 (1.00–1.21)
0≤0.61.4
Synonymous OE1.10
0≤1.21.6
LoF obs/exp: 28 / 28.6Missense obs/exp: 300 / 273.1Syn Z: -0.75
DN
0.81top 10%
GOF
0.7126th %ile
LOF
0.2191th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

212 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic10
VUS100
Likely Benign39
Benign9
Conflicting3
43
Pathogenic
10
Likely Pathogenic
100
VUS
39
Likely Benign
9
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
41
0
43
Likely Pathogenic
6
0
3
1
10
VUS
0
94
6
0
100
Likely Benign
0
7
10
22
39
Benign
0
4
2
3
9
Conflicting
—3
Total81056226204

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CFAP53 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients